The Human Heart Contains Distinct Macrophage Subsets with Divergent Origins and Functions
Autor: | Craig H. Selzman, Geetika Bajpai, Daniel Kreisel, Yongjian Liu, Stavros G. Drakos, Slava Epelman, Andrea L. Bredemeyer, Nicole R. Wong, Maarten Hulsmans, Matthias Nahrendorf, Caralin Schneider, Akinobu Itoh, Thirupura S. Shankar, Kory J. Lavine |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Adult
0301 basic medicine CCR2 Receptors CCR2 animal diseases Population Biology General Biochemistry Genetics and Molecular Biology Article Weight-Bearing Ventricular Dysfunction Left 03 medical and health sciences Immune system parasitic diseases medicine Macrophage Humans Ventricular remodeling education Receptor Heart Failure Inflammation education.field_of_study Myocardium Monocyte Macrophages hemic and immune systems Heart General Medicine medicine.disease 030104 developmental biology medicine.anatomical_structure Heart failure Immunology |
Zdroj: | Nature medicine |
ISSN: | 1546-170X 1078-8956 |
Popis: | Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2− and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2− and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2− macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2− and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2− and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart. Study of macrophage heterogeneity in human hearts reveals a subset of inflammatory macrophages that is associated with cardiac dysfunction in patients with heart failure. |
Databáze: | OpenAIRE |
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